Nephron最新文献

Given the exceptional evolution of pharmacological approaches to chronic kidney disease (CKD) management and their potential interactions with lifestyle, in this review, we describe the intersection of exercise and pharmacotherapy, and the possible role of exercise training as an adjunct management option to optimise glucose-lowering therapies (GLTs) in people living with diabetes and CKD. Exercise remains a cornerstone intervention for individuals living with CKD and diabetes, providing well-established benefits for cardiovascular health, metabolic regulation, and preservation of physical function. While GLTs, including sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs), offer significant promise, these pharmacologic advances must be contextualised within a broader lifestyle framework to achieve optimal outcomes. Exercise and GLTs share complementary mechanisms, such as improvements in insulin sensitivity, inflammation, and body composition. Yet, the synergistic potential of combining these interventions warrants further investigation through high-quality trials and mechanistic studies. Current evidence is encouraging but insufficient to confidently guide clinical practice. Future research should prioritise strategies that integrate pharmacotherapy with structured exercise programs, while accounting for patient-specific factors such as comorbidities, frailty, and functional limitations. Implementation science will be critical to translate these findings into routine care, leveraging multidisciplinary teams, digital health tools, and behavioural support. Ultimately, success will depend on integrative, person-centred care models that align pharmacologic and lifestyle interventions to enhance quality of life, reduce disease burden, and improve long-term outcomes for people with CKD and diabetes.

Background: Pre-emptive dose reduction of low-molecular weight heparins (LMWHs) is often utilised in those with chronic kidney disease (CKD) to prevent bioaccumulation. We report on the association of a pre-emptive dose reduction on anti-Xa range and its correlation with clinical outcomes.

Methods: We undertook a retrospective service evaluation of patients with CKD (eGFR < 30 ml/min/1.73m2) receiving therapeutic dose dalteparin. The primary exposure was dalteparin anti-Xa trough and peak. Primary outcomes were ISTH-defined clinically relevant bleeding, thrombosis and all-cause mortality within 90 days of LMWH initiation. A multivariate Cox proportional hazards model was employed to assess the relationship between anti-Xa levels and the incidence of bleeding and mortality.

Results: A total of 103 patients were identified over a two year period. Seventy-eight (75.7%) had anti-Xa monitoring done. Trough anti-Xa distribution was within target in 58 (75.6%). Patients on dialysis had a higher incidence of bleeding (19 vs 12, p < 0.05). Patients with bleeding had significantly higher median anti-Xa trough (0.26 vs 0.13 U/mL, p < 0.01). The median time to bioaccumulation was 19 days. In multivariate Cox models, only anti-Xa trough remained an independent association with bleeding (HR: 1.47 per 0.1 U/mL, 95 % CI: 1.05-2.15; p < 0.05). No associations with mortality were identified.

Conclusion: In this report, trough anti-Xa measurement of dalteparin is independently associated with bleeding in patients with CKD. Further prospective, larger studies are warranted to validate these results before it can be universally recommended in clinical practice.

In the article by Imberti and Benigni entitled "Renal Endowment in Men and Women: Start from the Beginning" [Nephron. 2025;149:207-212; https://doi.org/10.1159/000542411], the following statement was mistakenly left out of the Acknowledgements section:This review is based on lectures given by A.B. for the CME course of the DOKI project: "Gender Differences in Renal Disease: Focus on Diabetes and Obesity," Garachico - Tenerife (Canary Islands, Spain, December 1-2, 2023), an initiative of the DOKI project (Diabetes, Obesity and the Kidney) - PN: 101079207 - Twinning project, awarded by the European Commission.

Kidneys require large amounts of energy to maintain function, and are highly metabolically active. Acute kidney injury (AKI) and diseases including chronic kidney disease (CKD), diabetic kidney disease (DKD), and polycystic kidney disease (PKD) are strongly associated with metabolic disturbances. Whilst most research to date has focused on glucose and fatty acid metabolism, the catabolism of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine, is an emerging area of importance across different kidney pathologies. BCAAs can be used in protein synthesis, or catabolized to provide tricarboxylic acid (TCA) cycle intermediates. BCAAs and their metabolites can also act as signaling molecules. Disturbances of BCAA catabolism have recently been described in AKI, CKD, DKD, and PKD, driven by both transcriptional and post-translational mechanisms. This results in accumulation of BCAAs in the kidney and loss of a source of TCA cycle intermediates. In addition, accumulated BCAAs, especially leucine, can activate mechanistic target of rapamycin complex 1 (mTORC1) signaling. In addition to the described disturbances in BCAA catabolism, recent preclinical studies have shown that reactivation of BCAA catabolism could be a potential therapeutic strategy. This review will describe the process of BCAA catabolism, and its disturbances in AKI, CKD, DKD, and PKD.

Chronic hemodialysis therapy is a life-saving procedure requiring large amounts of water whereas this natural resource availability declines with increasing temperatures and the dialysis needs are far from being covered in many world areas. Reducing water consumption in hemodialysis relies on the moto "Reduce, Reuse and Recycle". Because of a significant amount of water is discarded to the drain by the procedure, the efficiency of the reverse osmosis (RO) of the water treatment system is a key factor of water consumption during the hemodialysis session. Along decades, the RO devices have become more efficient, with a decrease of the rejected part of water from around 70 to below 30%. The optimization of the maintenance and disinfection procedures of the water loop, as well as the practice of acid concentrate delivery to the dialysis machine can reduce significantly water needs. Reducing dialysate flow is also effective, even with convective modalities, but more studies are needed to confirm long-term patient safety. The co-decision with the patient on dialysis modality choice including alternatives to hemodialysis must take into account the environmental impact after appropriate information. Other aspects of water sparing are presented including, among others, the reuse of RO water reject and the spent dialysate recycling. Green dialysis including the water preservation must become a "top of the list" priority for all the dialysis stakeholders to preserve the future of this tremendous progress of medical history.

Background: Living donor kidney transplantation offers superior long-term outcomes compared to deceased donor transplantation. However, ensuring long-term donor safety remains the primary objective of the clinical assessment process. Pre-donation risk evaluation can be challenging, particularly in specific borderline scenarios where evidence is limited.

Summary: This review explores several critical aspects of the decision-making process in LKD assessment. It addresses how to evaluate potential donors with complex medical or psychosocial profiles, including those with obesity, advanced age, psychiatric histories, or past substance use. The review also emphasizes the importance of using accurate and reliable tools for donor evaluation, such as measured glomerular filtration rate (mGFR), particularly in cases with borderline kidney function, and discusses the growing role of genetic testing as it becomes more accessible. Furthermore, it considers how socioeconomic, cultural, and religious factors can influence both the willingness to donate and the likelihood of being selected as a donor. Lastly, the review underscores the essential role of long-term follow-up in safeguarding donor health and optimizing outcomes.

Key messages: To safely expand the pool of eligible living kidney donors, it is essential to use precise evaluation tools, ensure and enable long-term follow-up, and promote research to improve risk stratification and guide decision-making. In this review, we update information in the evaluation of living kidney donors highlighting gaps in current knowledge and practice.

: Background and Hypothesis: Monoallelic pathogenic variants in GANAB cause autosomal dominant cystic kidney and liver disease, but quantitative imaging phenotypes remain incompletely defined.

Methods: We performed a retrospective study of 16 individuals with GANAB variants and available abdominal imaging. Deep learning based-cyst segmentation quantified kidney and liver volumes and cyst metrics, including height-adjusted total kidney volume (htTKV), liver volume (htTLV), cyst number (TCN), and cyst volume (htTCV).

Results: Hepatic involvement was common, with polycystic liver disease present in most individuals with varying severity (liver TCN range 22 to 219). Kidney involvement was more heterogenous (htTKV range 153 to 858 mL/m; kidney TCN range 3 to 42). Individuals with kidney TCN <20 had preserved kidney function and slower annual eGFR decline (median -1.68 mL/min/1.73m2) compared with those with kidney TCN ≥20 (-2.8 mL/min/1.73 m2/year); no individual progressed to kidney failure during follow up. Hypertension occurred in 50%. Intracranial aneurysms were identified in 3 of 6 screened individuals, including two from a family with known aneurysmal disease.

Conclusions: Quantitative imaging reveals a phenotypic spectrum in ADPKD-GANAB, ranging from liver-predominant cystic disease with minimal kidney involvement to a phenotype with higher kidney cyst burden and faster eGFR decline. Establishing robust genotype-phenotype relationships in this rare disease will require larger, aggregated cohorts with standardized imaging and systemic extrarenal screening.

Background: In patients with chronic kidney disease (CKD), lower and sub-functional high-density lipoprotein cholesterol (HDL-C) is associated with poor cardiovascular outcomes. Notwithstanding such poor outcomes, the primary therapeutic target in patients with CKD is low-density lipoprotein cholesterol (LDL-C), and the comparative effectiveness of commonly used lipid-lowering therapies (LLTs) in changing HDL-C levels in patients with non-dialysis-dependent CKD (NDD-CKD) remains unclear.

Methods: In this retrospective cohort study, using a target trial emulation framework, we examined a nationwide cohort of 3,562,882 US Veterans with normal kidney function enrolled between October 2004 and September 2006 and identified 247,270 incident CKD patients eligible for de novo LLT exposure, occurring during longitudinal follow-up until October 2019. We defined de novo LLT initiation using pharmacy dispensation data and followed patients for up to 1 year. We compared the intraindividual slopes of HDL-C levels in de novo fibrates and niacin users with those in statin users, using mixed-effects models adjusted for baseline and time-varying covariates. We also compared the odds of having a clinically meaningful (>10% from baseline) increase in HDL-C following LLT initiation.

Results: A total of 38,223 patients with incident CKD initiated de novo LLT (statin [n=35,284], fibrate [n=1,805], and niacin [n=1,134]). The mean (SD) age was 67.3 (10.5) years; 95.0% were men, and 20.6% were Black. Compared to statin users, the multivariable-adjusted annualized intraindividual increase of HDL-C was significantly higher following fibrate (1.15 mg/dL/year [95% CI: 0.43, 1.87]; p=0.002) and niacin monotherapy (2.51 mg/dL/year [95% CI: 1.62, 3.41]; p<0.001). Furthermore, niacin (OR: 1.37 [95% CI: 1.07, 1.75]; p=0.012) was more likely than statins to provide a clinically meaningful elevation in HDL-C. Our findings were consistent in several sensitivity analyses.

Conclusion: Among patients with NDD-CKD, de novo prescription of fibrates and niacin is associated with a greater increase in HDL-C levels compared to statins. Further studies are warranted to investigate whether such differences have meaningful effects on clinical outcomes.

Introduction Pauci-immune necrotizing and crescentic glomerulonephritis (PiNCGN) is a leading cause of rapidly progressive kidney failure. Several prognostic tools-Berden classification, Mayo Clinic Chronicity Score (MCCS), Percentage of ANCA Crescents Score (PACS), ANCA Renal Risk Score (ARRS), and the improved ANCA Kidney Risk Score (AKRiS)-have been developed to predict renal outcomes, but data on their performance in ANCA-negative patients remain scarce. This study evaluated the prognostic value of these scoring systems in a PiNCGN cohort. Methods We retrospectively analyzed 100 patients with biopsy-proven PiNCGN. Demographic, laboratory, and histopathological data were collected, and patients were categorized according to all five risk scores. Outcomes included all-cause mortality and end-stage kidney disease (ESKD), defined as initiation of dialysis or kidney transplantation. Kaplan-Meier survival and log-rank tests were applied to assess prognostic discrimination. Results Of 100 patients, 86 were ANCA-positive and 14 ANCA-negative. Median age was 58.5 years; 41% were male. Induction therapy consisted of glucocorticoids with cyclophosphamide or rituximab, followed by azathioprine, mycophenolate, or rituximab for maintenance. Over a median follow-up of 12 months, 52 patients died and 21 progressed to ESKD. In ANCA-positive patients, ARRS and AKRiS best predicted ESKD. In ANCA-negative patients, AKRiS additionally predicted both mortality and ESKD. Other scores demonstrated limited utility. Conclusion ARRS and AKRiS provided the most consistent prognostic stratification in PiNCGN, with AKRiS uniquely retaining value in ANCA-negative patients. These findings highlight the potential clinical utility of composite scoring systems across the spectrum of PiNCGN, although prospective multicenter validation remains warranted.